This report contains results of studies designed to determine whether quinine has direct effects on myofilament Ca2+ sensitization in addition to effects on Ca2+. Quinine decreased the EC50 value and maximal contraction of intact arterial strips to histamine. Incubation of arterial strips with indomethacin or 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one did not alter quinine inhibition, sugg...

Reduction in electron transport is associated with decreased production in alpha-toxin despite the fact that Staphylococcus aureus is able to grow from 1 CFU to >10(7) CFU. Similarly, under anaerobic conditions, S. aureus does not produce alpha-toxin. Although the pathways that connect oxidative metabolism and toxin production are unknown, agents are available that exhibit greater inhibition of...

Tetanus neurotoxin (molecular weight approximately 160,000) was purified from bacterial extracts (intracellular toxin) and mildly trypsinized and from culture filtrates (extracellular toxin). Both purified preparations could be dissociated reversibly into two polypeptide chains, with molecular weights of 53,000 (fragment alpha) and 107,000 (fragment beta), by treatment with 100 mM dithiothreito...

Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific antisera to identify the protein in tissues and to assay it during purification from bovine brain. Additionally, expression of the cDNA in Escherichia coli has resulted in the production and purification ...

BACKGROUND B. anthracis anti-toxin agents are approved and included in the Strategic National Stockpile based primarily on animal infection trials. However, in the only anthrax outbreak an approved anti-toxin agent was administered in, survival did not differ comparing recipients and non-recipients, although recipients appeared sicker. OBJECTIVE Employ a systematic review and meta-analysis to...

Chimaeric toxins have considerable therapeutic potential to treat various malignancies. We have previously used the fungal ribonucleolytic toxin restrictocin to make chimaeric toxins in which the ligand was fused at either the N-terminus or the C-terminus of the toxin. Chimaeric toxins containing ligand at the C-terminus of restrictocin were shown to be more active than those having ligand at t...

A novel HERG channel blocker was isolated from the venom of the scorpion Buthus martensi Karsch, sequenced and characterized at the pharmacological level after chemical synthesis. According to the determined amino acid sequence, the cDNA and genomic genes were then cloned. The genomic gene consists of two exons interrupted by an intron of 65 bp at position -6 upstream from the mature toxin. The...

The effects of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) on parathyroid hormone (PTH)-responsive adenylate cyclase were examined in clonal rat osteosarcoma cells (UMR-106) with the osteoblast phenotype. Recombinant TFG-alpha and EGF incubated with UMR-106 cells for 48 h each produced concentration-dependent inhibition of PTH-responsive adenylate cyclase, wit...

NHE3 activity is regulated by phosphorylation/dephosphorylation processes and membrane recycling in intact cells. However, the Na(+)/H(+) exchanger (NHE) can also be regulated by G proteins independent of cytoplasmic second messengers, but the G protein subunits involved in this regulation are not known. Therefore, we studied G protein subunit regulation of NHE3 activity in renal brush-border m...

Noradrenaline- and clonidine-induced inhibition of insulin release from intact and electrically permeabilized rat islets was markedly relieved by prior exposure to 100 ng of Bordetella pertussis toxin/ml. The reversal of catecholamine inhibition of insulin secretion by this toxin was not associated with a decrease in specific binding of the alpha 2-adrenergic ligand [3H]yohimbine, and could not...